CAR T-Cell Therapy Offers Hope for Lasting Remission in Hairy Cell Leukemia

After almost four decades of living with hairy cell leukemia, a 68-year-old man had run out of reliable treatment options. His cancer had returned despite multiple rounds of therapy, and a mass near his bladder had grown large enough to interfere with drainage from his right kidney.

Previous treatments, including chemotherapy, targeted drugs and the removal of his spleen, had failed to keep the cancer under control. A combination of vemurafenib and rituximab initially helped, but the response lasted only a few months.

Then he received an experimental CAR T-cell therapy at the National Institutes of Health (NIH).

More than two and a half years later, doctors have found no detectable trace of his leukemia, according to Dr. Robert J. Kreitman, senior investigator and head of the Clinical Immunotherapy Section at the National Cancer Institute (NCI).

"We can't say that patient's cured," Kreitman said. "But we have no trace of any hairy cell anywhere in that patient."

The patient's response offers a glimpse into what may be possible for people with relapsed or refractory hairy cell leukemia, a rare blood cancer that often responds well to initial treatment but can return years later.

For Kreitman, who has spent decades developing treatments for the disease, the goal extends beyond helping patients achieve remission. He wants to eliminate the cancer cells that remain after treatment and may eventually cause the disease to return.

Targeting Leukemia That Keeps Coming Back

Hairy cell leukemia is a rare cancer of B lymphocytes, a type of white blood cell. Its name comes from the hairlike projections visible on the surface of cancer cells under a microscope.

Standard treatments such as cladribine and pentostatin can produce long-lasting remissions. However, some patients eventually relapse and require additional treatment.

A 2025 study published in JCO Precision Oncology, led by Kreitman, noted that the median time to relapse following treatment with these drugs has ranged from 4.5 to 16 years across previous studies. Although retreatment can be effective, repeated therapies may bring additional toxicities and shorter periods of remission.

The challenge becomes greater for patients whose leukemia no longer responds to available treatments.

Kreitman and his colleagues are investigating whether chimeric antigen receptor (CAR) T-cell therapy could provide another option.

Unlike conventional chemotherapy, CAR T-cell therapy uses a patient's own immune cells. T cells are collected from the blood, genetically modified to recognize a specific protein on cancer cells and infused back into the patient to attack the disease.

The investigational therapy targets CD22, a protein found in high amounts on hairy cell leukemia cells.

"CD22 is a very good antigen for hairy cell leukemia," Kreitman explained.

His research found that hairy cell leukemia cells have substantially more CD22 binding sites than cells from B-cell acute lymphoblastic leukemia, another cancer in which CD22-targeted CAR T-cell therapy has been studied.

What Early Research Has Found

In the phase 1 clinical trial, researchers are evaluating the safety and preliminary effectiveness of CD22-directed CAR T-cell therapy in patients with relapsed or refractory hairy cell leukemia, including the variant form of the disease.

The initial published findings included four heavily pretreated patients.

The first two patients received a lower dose of CAR T cells and did not experience significant responses. Researchers subsequently increased the dose for the next two participants.

Of those two patients, one experienced a substantial reduction in leukemia cells but developed serious treatment-related complications. The other achieved a complete remission with no detectable minimal residual disease, or MRD.

MRD refers to the small number of cancer cells that may remain after treatment, even when a patient appears to be in remission. These cells can be difficult to identify through routine testing but may eventually lead to relapse.

The patient who achieved complete remission had lived with hairy cell leukemia for 38 years. Before entering the trial, his disease had spread beyond the blood and bone marrow, forming masses in several areas of his body.

Following CAR T-cell treatment, imaging showed that those masses gradually cleared. By six months, scans showed no remaining metabolically active lesions, and subsequent biopsies confirmed no detectable leukemia in a previously affected mass.

The researchers reported that he remained in remission at the one-year follow-up. During his more recent interview, Kreitman said the patient had continued without detectable disease for more than two and a half years.

The results are encouraging, although the study's small size means researchers cannot yet determine how many patients might benefit or how long their responses will last.

Why the Amount of Cancer Matters

One of the most important findings from Kreitman's research concerns the amount and location of leukemia in a patient's body before CAR T-cell therapy.

The two patients who received the higher CAR T-cell dose had markedly different outcomes.

One had a high number of leukemia cells circulating in his blood and extensive disease in his bone marrow. Although treatment dramatically reduced the number of cancer cells, he developed severe immune-related toxicity, including a life-threatening inflammatory condition.

The other patient had little detectable leukemia in his blood or bone marrow at the time of infusion, although cancerous masses remained elsewhere in his body. His treatment produced a complete response with substantially less toxicity.

Kreitman explained that when CAR T cells encounter large numbers of cancer cells, the resulting immune response can become overwhelming.

These reactions may include cytokine release syndrome, a condition in which the immune system releases large amounts of inflammatory substances. Severe complications can also involve neurologic symptoms or excessive activation of immune cells.

However, Kreitman said his team's experience suggests that CAR T-cell therapy may be particularly useful for patients whose disease is concentrated in masses outside the blood and bone marrow.

"We can see gradual clearing of those solid masses with essentially no significant toxicity to the patient with CAR T," he said.

The findings have important implications for future treatment planning.

Rather than reserving CAR T-cell therapy until patients have exhausted every available option and their disease has progressed extensively, Kreitman believes some patients may benefit from considering the treatment earlier.

Researchers are also examining whether other therapies could first reduce the number of circulating leukemia cells before CAR T-cell infusion, potentially lowering the risk of serious complications.

Moving Beyond Remission Toward a Cure

Kreitman's interest in eliminating residual leukemia began long before the current CAR T-cell trial.

In 1983, he first encountered hairy cell leukemia while training under Dr. Bertha Bouroncle, who had helped identify the disease decades earlier.

Later, while working with Dr. Ira Pastan at the NCI, he began investigating experimental drugs known as immunotoxins, which combine an antibody that recognizes cancer cells with a toxin designed to destroy them.

That work eventually contributed to the development of moxetumomab pasudotox, marketed as Lumoxiti, which received FDA approval in 2018 for certain patients with relapsed or refractory hairy cell leukemia. The manufacturer subsequently withdrew the drug from the market.

Kreitman said the immunotoxin and CAR T-cell approaches may have complementary advantages.

Lumoxiti showed strong activity against leukemia in the blood, bone marrow and spleen, while the CAR T-cell therapy being studied may be especially useful against masses of leukemia elsewhere in the body.

The broader goal is to develop treatments that do more than temporarily reduce the amount of cancer.

Kreitman pointed to a patient treated with an earlier immunotoxin, BL22, more than 25 years ago who continues to show no detectable evidence of hairy cell leukemia.

"We think it can be, but it's going to take many, many years to determine that," Kreitman said when asked whether the disease could be cured.

For patients who achieve complete remission, the distinction between controlling the disease and eliminating it entirely may be especially important.

"If left alone, MRD eventually will cause relapse. That is what we have seen," he said.

Still, undetectable MRD does not automatically establish a cure, and longer follow-up is needed to determine whether CAR T-cell therapy can prevent future relapse.

What Comes Next for Patients?

The ongoing phase 1 trial (NCT04815356) continues to investigate CD22-directed CAR T-cell therapy in patients with relapsed or refractory hairy cell leukemia and its variant.

Kreitman's team is also studying other targeted treatments, including drugs that inhibit BRAF, BCL2 and BTK, to expand options for patients whose disease returns.

For now, CAR T-cell therapy remains investigational for hairy cell leukemia, and the results cannot yet be generalized to all patients.

Kreitman emphasized that it should not be confused with a stem cell transplant. CAR T-cell therapy uses a patient's own modified immune cells and does not carry the graft-versus-host disease risk associated with donor stem cell transplantation, although it has its own potentially serious side effects.

He hopes that continued research will help establish when patients are most likely to benefit, how risks can be reduced and whether the responses observed so far can last for decades.

For the patient who remains free of detectable leukemia more than two and a half years after treatment, those questions are still unanswered.

But after decades of recurring disease, the possibility of a lasting remission offers a reason for optimism.

"We think it could be a cure," Kreitman said.

References

1. Kreitman RJ, et al. Complete response in hairy cell leukemia to anti-CD22 CAR T-cell therapy. JCO Precision Oncology. 2025.

2. Kreitman RJ, et al. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia. 2018.

3. Kreitman RJ, et al. Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox. Blood. 2018.

4. National Cancer Institute. Anti-CD22 CAR T cells in patients with relapsed/refractory hairy cell leukemia and variant hairy cell leukemia. ClinicalTrials.gov. NCT04815356.

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